SU1538892A3 - Method of producing tritherphenyl esters of organic acids - Google Patents

Abstract

The invention relates to unsaturated cycloaliphatic substances, in particular triterpenyl esters of acids of general formula I: CH = CH-CR ₁ = CR ₂ -CR ₃ = CR ₄ , where R ₁ = C (O) OR ₆

CH = CR ₅ -C (O) OR ₆

R ₂ = H, OH

R ₃ = H, OH, C ₁ -C ₄ -alkyl group, R ₄ = H, OH, NH ₂

R ₅ = H, C ₁ -C ₄ -alkyl

R ₆ -cycloartenyl, cyclobranyl, 24-methylenecycloartanyl, and the substitution in the benzene cycle may be a pair selected from the series: a) OH and C ₁ -C ₄ alkoxy

b) NH ₂ and C ₁ -C ₄ -alkoxygroup

c) two OH groups, with the exception of ferulic acid triterpenyl esters, or d) at least one of R ₂ -R ₄ = OH, or e) R ₄ = NH ₂ , which have anti-thyroid effect, which can be used in medicine. The goal is to create more active substances of the specified class. Synthesis is carried out by deacylation of the triterpenyl alcohol ester of f-ly II: CH = CH-CR ₁ = CR ₇ -CR ₈ = CR ₉ , where R ₁ is above, R ₇ = H, C ₂ -C ₆ is acyloxy

R ₈ = H

C ₁ -C ₄ - alkoxy- or C ₂ -C ₆ -acyloxy

R ₉ = H, C ₂ -C ₆ -acyloxy, C ₂ -C ₅ -acylamido, and the substitution in the benzene cycle can be a pair selected from the series: a) C ₂ -C ₄ -acyloxy and C ₁ -C ₄ alkoxy

b) C ₂ -C ₅ -acyl and C ₁ -C ₄ -alkoxy-

c) two C ₂ -C ₆ acyloxy, d) one of R ₇ -R ₉ = C ₂ -C ₆ acyloxy

d) R ₉ -acyl-C ₂ -C ₅ group. New substances

Description

form (200 ml). The solution is washed with a saturated aqueous solution of sodium bicarbonate. The aqueous layer was extracted with chloroform (3 x 200 ml). The combined extracts are dried and concentrated, then crystallized by adding ethanol, resulting in the production of cycloartenyl-4-hydroxy-3-methoxy-benzoate containing molecular ethanol (21.0 g), yield 87%, mp 132 ° WITH.

W

2 &

61.3

Specific rotation (from 1.00, СНС1,).

Calculated,%: C 77.12; H 10.03.

C38 H5WO ,,. (Mol.m. 622.90)

Found,%: C 77.21; H 10.12.

IR (KBr), cm-1: 3380, 2920, 2850 1705, 1683, 1607, 1590, 1510, 1280, 1225.

Poland (CDCl1), S: 0.39 (1H, 1/2 AV sq., 4.2 Hz); 0.60 (1H, 1/2 AV sq., 4.2 Hz); 0.70-2.40 (27H, m); 0.91 (6H, s); 0.97 (3N, s); 1.03 (3N, s); 1.60 (ZN, sh. S); 1.68 (ZN, sh. S); 3.93 (ЗН, s); 4.60-5.30 (2H, m); 6.08 (1H, bhp); 6.78-7.80 (ЗН, m).

PRI me R 9. Cyclobranyl-3,4-dihydroxycinnamate.

a) Preparation of cyclobranyl-3,4-dipropionyloxycinnamate.

17.43 ml of thionyl chloride (2 eq.) Was added to a suspension of 3,4-dipropionyl caffeic acid (35.07 g, 0.12 mol) in toluene (150 ml), and the reaction mixture was stirred at 60 ° C for 2 hours. The resulting mixture was distilled under reduced pressure to remove the solvent. The residue was suspended in a mixture of toluene (240 ml and pyridine (50 ml). Cyclobranol (40 g, 0.0908 mol) was added to this suspension, and the mixture was stirred at 60 ° C for 2 hours. Then the solvent was distilled off - underpressure. The residue is extracted with chloroform (300 ml).

five

0

five

0

five

0

Calculated,%: C 77.27; H 9.30.

C4ЈHfc6 ° & (mol.m. 714.99)

Found,%: C 77.34; H 9.23.

IR (KBG)}, 2920, 2850, 1770, 1710, 1250, 1170.

PMR (CDC1,), S: 0.36 (1H, 1/2 AV sq., 4.8 Hz); 0.62 (1H, 1/2 AVQ 4.8 Hz); 0.70-2.20 (27H, m); 0.90 6H, s); 0.96 (6H, s); 1.25 (6H, t, 7.2 Hz); 1.62 (9H, s); 2.57 (4H, q, 7.2 Hz); 4.50-4.88 (1H, m); 6.36 (1H, 1/2 AV sq., 16.6 Hz); 7.05 (ЗН, m); 7.60 (1H, 1/2 AV sq., 15.6 Hz).

b) Preparation of cyclobranyl-3,4-dioxycinnamate.

Cyclobranyl-3,4-dipropionyloxy cinnamate (35 g, 0.049 mol) obtained in step a is dissolved in diocean (600 ml). To this solution, 25% aqueous ammonia (70 ml) was added and the mixture was stirred at 50 ° C for 2 hours. Then the solvent was distilled off under reduced pressure. The crude crystals are recrystallized from acetone-water (4: 1, v / v) to obtain 22.3 g of cyclobranyl-3, 4-dioxycinnamate, 75% yield, i.e. 246-247.5 ° C.

(with

Specific rotation e / lc + 33.6

five

0

five

 1.10, СНС13).

Calculated,%: C 79.69; H 9.70.

C HgeO-v (mol.m. 602,86)

Found,%: C 79.62; H 9.68.

IR (KBG)}, 3400, 2920, 2850, 1680, 1600, 1520, 1440, 1275, 1180, 970.

PMR (CDC1 j), 8: 0.36 (1H, 1/2 AV sq., 4.8 Hz); 0.59 - (1H, 1 / 2AVq., 4.8 Hz); 0.69-2.20 (27H, m); 0.85 (3N, .c); 0.90 (30N, s); 0, U6 (6H, s); 1.60 (9H, s); 4.36-4.80 (1H, m); 6.16 (1H, 1/2 AV sq., 15.6 Hz), 6.60-7.16 (5H, m); 7.74 (1H, 1/2 AV sq., 15.6 Hz).

PRI me R 10. Getting cyclobranyl-3, 4-dioxycinnamate.

The proposed compound is prepared according to Example 96, where cyclobranyl-3,4-diacetoxycinnamate (35 g, 0.051 mol) is used instead of cyclobranyl-3,4-dipropionyloxycinnamate. Yield 22.1 g (64%), m.p. 246-247 ° C.

Specific rotation + 33.6 ° (with 0.11, CHClj).

Calculated,%: C 79.69; H 9.70.

С + 0К6804 (mol.m. 602,86)

Found,%: C 77.78; H 9.62.

Example 11. Cyclobranyl-4-hydroxy-3-methoxybenzoate.

a) Preparation of cyclobranyl-4-acetoxy-3-methoxybenzoate.

To 4-acetylvanilic acid (18.60 g, 0.0885 mol) dissolved in toluene (100 ml), thionyl chloride (12.86 ml, 2 eq.) Is added and stirred at 60 ° C for 2 h. The resulting mixture was evaporated under reduced pressure, and the residue was dissolved in toluene (150 ml) and pyridine (30 ml). Cyclobranch (30 g, 0.068 mol) was added to the resulting solution, and the mixture was stirred at 60 ° C for 2 hours, then evaporated under reduced pressure, and the residue was extracted with chloroform (300 ml). The extract obtained is dried, concentrated in vacuo and purified on a chromatography column with silica gel (solvent-ethyl acetate: hexane 1: 6, v / v), resulting in an ester of cyclobranyl-4-acetoxy-3-methoxybenzoate (33.38 d)

yield 77%, so pl. 177-178 C.

about

2 (, 5

54, f

Specific rotation (with 1.02, СНС13).

Calculated,%: C 77.80; H 9.56.

C4iH6005 (mol.m. 632.89)

Found,%: C 77.71, H 9.64

IR (KBG)}, cm-: 2920, 2850, 1770.1710, 1285, 1190, 1170.

PMR (CDClj), $: 0.38 (1H, 1/2 AV sq., 4.8 Hz); 0.63 (1H, 1/2 AV sq., 4.8 Hz); 0.70-2.40 (27H, m); 0.92 (6H, s); 0.98 (3N, s); 1.04 (ЗН, s); 1.62 (9H, s); 2.32 (ЗН, с) 3.83 (ЗН, с); 4.60-5.00 (1H, m); 6.92-7.20 (1H, m); 7.51-7.80 (2H, m).

b) Preparation of cyclobranyl-4-hydroxy-3-methoxyben-zoate.

Cyclobranyl-4-acetoxy-3-methoxy benzoate (30 g, 0.0474 mol) obtained in step a is dissolved in tetrahydrofuran (300 ml) and a 25% solution is added to the resulting solution

15

20 30

25

50

55

aqueous ammonia (60 ml). The resulting mixture was stirred at 50 ° C for 2 hours, then evaporated to dryness under reduced pressure. The remaining crystals are recrystallized from acetone-water (5: 1, v / v) to obtain cyclobyl-4-hydroxy-3-methoxybenzoate (23.1 g),) 0 yield 82%, mp. 191-193 ° C.

Specific rotation & + 55.8 ° (c 1.02, CHClj).

Calculated,%: C 79.27; H 9.89. C, 9H5804 (mol.m. 590.85) Found,%: C 79.35; H 9.80. IR (KBG)}, 3400, 2920, 2850, 1700, 1590, 1510, 1275, 1220.

PMR (CDC13), S: 0.38 (1H, 1/2 AV sq., 4.8 Hz); 0.64 (1H, 1/2 AVQ., 4.8 Hz); 0.70-2.2 (27H, m); 0.92 (6H, s); 1.00 (3N, s); 1.05 (ЗН, s); 1.64 (9H, s); 3.95 (ЗН, s); 4.6-5.0 (1H, m); 6.06 (1H, bhp); 6.74-7.04 (1H, m); 7.44-7.77 (2H, s).

PRI me R 12. Cyclobranyl-3,4-hydroxybenzoate.

a) Preparation of cyclobranyl-3,4-di-acetoxybenzoate.

Thionyl chloride (12.86 ml, 2 eq.) Was added to diacetylprotocatechic acid (21.08 g, 0.085 mol) suspended in toluene (100 ml) and stirred for 2 hours. Then the mixture was evaporated under reduced pressure. pressure. The residue was suspended in toluene (150 ml) and pyridine (30 ml), and cyclobranol (30 g, 0.068 mol) was added to the suspension. The resulting mixture was stirred at 60 ° C for 2 hours. The resulting solution was then evaporated under reduced pressure. The residue is extracted with chloroform (300 ml). The extract obtained is dried, concentrated in vacuo and purified on a chromatographic column with silica (solvent-toluene), resulting in a cyclobranyl-3,4-diacetoxybenzoate (24.2 g), yield 54%, m.p. 165-166 ° C.

The specific rotation is otj 51.3 ° (c 1.01, СНС1,).

Calculated,%: C, 76.32; H 9.15. C42.Hto ° 5 (mol.m. 660.90) Found,%: C 76.45; H 9.10. IR (KBG), 2920, 2850, 1770, 1715, 1280, 1195, 1160.

PMR (CDC13), S: 0.36 (1H, 1/2 AV sq., 4.8 Hz); 0.62 (2H, 1 / 2ABB,

35

40

45

4.9 Hz); 0.70-2.40 (27H, m); 0.90 (6H, s); 0.96 (3N, s); 1.00 (3N, s) 1.60 (9H, s); 2.26 (6H, s); 4.60 - 4.98 (1H, m); 7.08-7.40 (1H, s); 7.73-8.06 (2H, m).

b) Preparation of cyclobranyl-3,4-dioxybenzoate.

Cyclobranyl-3,4-diacetoxybenzoa (24.0 g, 0.0363 mol) obtained in step a is dissolved in dioxane (480 ml) and 25% aqueous ammonia (48 ml) is added to this solution. The resulting mixture is stirred for 1 hour, then evaporated to dryness under reduced pressure. The remaining crystals are recrystallized from ethanol, resulting in the formation of cyclobranyl-3,4-dioxy

benzoate (17.5 g), yield 84%, mp 21 216 ° С.

The specific rotation is utj26 + 59.4 ° (c 0.98, СНСЬ).

Calculated,%: C 79.12; H 9.79.

C38H56 ° 4 (mol.m. 576.83}

Found,%: C, 79.03} H, 9.87.

IR (KVgN, cm-1: 3350.2920.2850 1680, 1605, 1440, 1280, 1230, 1100, 875.

PMR (CDC13), S: 0.38 (1H, 1/2 AV sq., 4.9 Hz); 0.61 (1H, 1/2 AV sq., 4.8 Hz); 0.70-2.20 (27H, m); 0.90 (6H, s); 0.98 (3N, s); 1.02 (3N, s) 1.62 (9H, s); 2.72-3.20 (2H, ws); 4.60-4.90 (1H, m); 6.70-6.96 (1H, m) 7.40-7.64 (2H, m).

Example 13. Cyclobranyl-ortho-hydroxybenzoate.

a) Preparation of cyclobranyl-ortho-acetoxybenzoate.

Thionyl chloride (40 ml, 6.3 eq.) Is added to acetylsalicylic acid (15.94 g, 0.088 mol) suspended in toluene (100 ml) and the mixture is evaporated under reduced pressure, the residue was dissolved in toluene (180 ml) and pyridine (40 ml), and then cyclobra (30 g, 0.068 mol) was added. The resulting mixture was continued to stir at 60 ° C for 2 hours, and then evaporated under reduced pressure. The residue is extracted with chloroform (300 m and the extract is washed with 3% aqueous sodium bicarbonate, water and saturated brine. The resulting extract is dried, concentrated in vacuo and the resulting residue is purified

a silica gel gel column (solvent-hexane: toluene 1: 1, v / v), resulting in a cyclobranyl-ortho-acetoxybenzoate (29.6 g), yield 72%, mp. 165-166 ° C. Specific rotation of geo + 58.4 y (from 1.01, СНС1,).

Calculated,%: C 79.69; H 9.70. С4оИ58 ° 4 (mol.m. 602,86)

Found,%: C 79.64; H 9.78.

IR (KVGI,: 2920, 2850, 1770, 1720, 1260, 1190, 1080.

PMR (CDC1,), S: 0.36 (1H, 1/2 AV sq., 4.8 Hz); 0.60 (1H, 1/2

AB squ., 4.8 Hz); 0.70-2.40 (27H, m); 0.89 (6H, s); 0.96 (3N, s); 1.00 (3N, s); 1.62 (9H, s); 2.33 (3N, s); 4.60-4.95 (1H, m); 6.88-7.68 (ЗН, m);

7.82-8.10 (1H, m)

five

steps a, dissolved in 400 ml of dioxane, and 25% aqueous ammonia (60 ml) was added dropwise to the resulting solution. The mixture was stirred at 50 ° C for 2 hours and evaporated to dryness under reduced pressure. The remaining crystals recrystallized from a mixture of acetone and water (1: 1, v / v), resulting in the cyclobranyl-ortho-hydroxybenzoate ester

J

0 7.82-8.10 (1H, m)

b) Preparation of cyclobranyl-ortho-hydroxybenzoate.

Cyclobranyl-ortho-acetoxybenzoate (24 g, 0.0398 mol) obtained on

0

five

(20.2 g), 90% yield, m.p. 200-201 s.

Specific rotation li + 69.3 (with 1.00, СНС1,).

Calculated,%: C 81.38; H 10.07.

SZVN56 ° (mol.m. 560, 83)

Found,%: C 81.29; H 10.02.

IR (KBr) l,: 3120.2920, 2850, 1670, 1615, 1300, 1250, 1220, 1165, 1095.

PMR (CDC13), S: 0.37 (1H, 1/2 AV sq., 4.8 Hz); 0.62 (1H, 1 / 2AB, square 4.8 Hz); 0.7-2.20 (27H, m); 1.05 (3N, s) 0.90 (6H, s); 0.97 (3N, s); 1.60 (9H, s); 4.60-5.00 (1H, m); 6.67-7.93 (4H, s); 10.92 (1H, s).

PRI me R 14. Cyclobranyl-para-aminobenzoate.

a) Preparation of cyclobryl-para-acetamido benzoate.

Thionyl chloride (25.7 ml, 4 eq.) Is added to para-acetamido-benzoate acid (15.85 g, 0.088 mol) dissolved in dioxane (150 ml) and stirred at 60 ° C for J2 h.

0

The mixture was evaporated under reduced pressure, and dioxane (150 ml) and pyridine (50 ml) were added to the residue. Cyclobranol (30 g, 0.069 mol) was added to the resulting solution, and the mixture was stirred at 60 ° C for 2 hours. The reaction mixture was evaporated under reduced pressure, and ethyl acetate (300 ml) was added to the residue. The crude crystals are isolated by filtration and purified on a chromatographic column with silica gel (solvent-chlorine

a) Preparation of cyclobranyl-para-acetoxyben zoate

para-Acetoxybenzoic acid (18.6 g, 0.103 mol) and thionyl chloride (40 ml) were mixed and stirred for 12 hours. Then, excess thionyl chloride was removed by distillation under reduced pressure. Cyclobranol (35 g, 0.0794 mol) is added to this residue suspended in toluene (220 ml) and pyridine (60 ml) and stirred at 60 ° C for 2 hours. Then the solution

forms). The obtained crystals are re-evaporated under reduced pressure, tallysed from ethanol, as a result of which cyclobranyl-para-acetamidobenzoate (32 g) is obtained, yield 78%, mp. 197-198 ° C.

Specific rotation Јji) + 54.7 °

(c 1.01, CHCl j).

Calculated,%: C 79.82; H 9.88;

N 2.32.

C40HS03N (mol.m. 601.88)

Found,%: C 79.75; H 9.83, N 2.41.

IR (KBr), 3420, 2920, 28-50, 1710, 1690, 1680, 1600, 1535, 1280, 1175.

NDP (CDC1}), 8: 0.38 (1H, 1/2 AV sq., 4.8 Hz); 0.62 (1H, 1/2 AV sq., 4.8 Hz); 0.70-2.28 (27H, m); 0.90 (6H, s); 0.98 (3N, s); 1.04 (ЗН, s); 1.62 (9H, s); 2.16 (3N, s); 4.50-4.96 (1H, m); 7.37 (1H, bhp); 7.44-8.12 (4H, m).

b) Preparation of cyclobranyl-para-aminobenzoate.

Cyclobranyl-para-acetamido-benzoate (32 g, 0.053 mol) obtained in step a is dissolved in tetrahydrofuran (300 ml), then concentrated hydrochloric acid (60 ml) is added and stirred at 70 ° C for 2 hours The mixture is evaporated under reduced pressure. The residue is extracted with chloroform (400 ml), then the resulting extract is dried and concentrated. The residue is purified twice on a chromatographic column with silica gel (solvent is a mixture of toluene, hexane ethyl acetate 5: 3: 1, volume / volume), resulting in a cyclobranyl-para-aminobenzoate (17 g), yield 57%, mp. 190-19GS.

The specific rotation is O26 + 58.4 ° (c 1.01, CHClj). D

Example 15. Cyclobranyl-p-hydroxybenzoate.

20

25

thirty

35

40

and the residue obtained is extracted with chloroform (400 ml). The extract obtained is dried and concentrated in vacuo, and the product obtained is purified on a chromatographic column with silica gel (chloroform solvent), resulting in the preparation of cyclobranyl-para-acetoxybenzoate ester (44.1 g), yield 92%, mp. . 192-193 ° C. 2g

The specific rotation is cij + 55.5 ° (c 0.93, CHClj).

Calculated,%: C 79.69; N.

С40Н560 |. (mol.m. 602-86)

Found,%: C 79.61; H 9.79.

IR (KBG)}, cm-: 2920, 2850, 1765, 1715, 1270, 1190, 1160, 1115.

PMR (CDC1), S: 0.36 (1H, 1/2 AV sq., 4.8 Hz); 0.60 (1H, 1/2 AV sq., 4.8 Hz); 0.68-2.40 (27H, m); 0.89 (6H, s); 0.96 (3N, s); 1.01 (3N, s); 1.60 (9H, s); 2.28 (3N, s); 4.60-5.00 (1H, m); 6.96-7.32 (2H, m) 7.90-8.25 (2H, m).

b) Preparation of cyclobranyl-para-hydroxybenzoate.

Cyclobranyl-para-acetoxybenzoate (24 g, 0.0398 mol) obtained in step a was dissolved in tetrahydro45 furan (350 ml) and 25% aqueous ammonia (50 ml) was added. The resulting mixture was continued to stir at 40 | JC for 1 h, and then evaporated to dryness under reduced pressure.

50 The remaining crystals are recrystallized from ethanol, as a result of which cyclobranyl-para-oxibenzoate (21.0 g) is obtained in a yield of 94%, mp. 174-175 C.

55 Specific rotation VJjj + 57.7 (c 1.10, СНС1Э).

Calculated,%: C 79.16; H 10.30. C38 H56 0} CgH5ON (mol.m. 606.9)

 evaporated under reduced pressure,

20

five

0

five

0

and the residue obtained is extracted with chloroform (400 ml). The extract obtained is dried and concentrated in vacuo, and the product obtained is purified on a chromatographic column with silica gel (chloroform solvent), resulting in the preparation of cyclobranyl-para-acetoxybenzoate ester (44.1 g), yield 92%, mp. . 192-193 ° C. 2g

The specific rotation is cij + 55.5 ° (c 0.93, CHClj).

Calculated,%: C 79.69; N.

С40Н560 |. (mol.m. 602-86)

Found,%: C 79.61; H 9.79.

IR (KBG)}, cm-: 2920, 2850, 1765, 1715, 1270, 1190, 1160, 1115.

PMR (CDC1), S: 0.36 (1H, 1/2 AV sq., 4.8 Hz); 0.60 (1H, 1/2 AV sq., 4.8 Hz); 0.68-2.40 (27H, m); 0.89 (6H, s); 0.96 (3N, s); 1.01 (3N, s); 1.60 (9H, s); 2.28 (3N, s); 4.60-5.00 (1H, m); 6.96-7.32 (2H, m); 7.90-8.25 (2H, m).

b) Preparation of cyclobranyl-para-hydroxybenzoate.

Cyclobranyl-para-acetoxybenzoate (24 g, 0.0398 mol) obtained in step a was dissolved in tetrahydrofuran (350 ml) and 25% aqueous ammonia (50 ml) was added. The resulting mixture was continued to stir at 40 | JC for 1 h, and then evaporated to dryness under reduced pressure.

The remaining crystals are recrystallized from ethanol, as a result of which cyclobranyl-para-hydroxybenzoate (21.0 g) is obtained in a yield of 94%, mp. 174-175 C.

The specific rotation VJjj + 57.7 (c 1.10, СНС1Э).

Calculated,%: C 79.16; H 10.30. C38 H56 0} CgH5ON (mol.m. 606.9)

23

Found,%: C 79.13; H 10.42.

IR (KBG)}, 3400, 2920, 2850, 1685, 1610, 1280, 1160.

IMP (CDC1,), 5: 0.38 (1H, 1 / 2AB Apt, 4.8 Hz); 0.64 (1H, 1/2 AV sq., 4.8 Hz); 0.70-2.24 (27H, m); 0.91 (6H, s); 0.98 (3N, s); 1.02 (ЗН, s); 1.28 (3N, t, 7.2 Hz); 1.62 (9H, s); 3.77 (2H, q, 7.2 Hz); 4.60-5.00 (1H, m); 6.72-7.18 (4H, m); 7.80 - 8.12 (2H, m).

Approx 16. Cycloartenyl-3-ethoxy-4-hydroxybenzoate.

a) Preparation of cycloartenyl-acetoxy-3-ethoxybenzoate.

The proposed compound is prepared according to Example 8a, where 4-acetoxy-3-ethoxybenzoic acid (13.9 g, 0.062 mol) is used instead of 4-acetoxy-3-methoxybenzoic acid (13.0 g). Cycloartenyl-4-acetoxy-3-ethoxy-benzoate g (yield 82%) is obtained. 140-141 ° C.

Specific rotation G +58.2 (with 1.00, СНС13).

Calculated,%: C 77.80; H 9.56.

with inbo ° 5 (mol.m. 632.89)

Found,%: C 77.91; H 9.43,

b) Preparation of cycloartenyl-3-ethoxy-4-hydroxybenzoate.

Cycloartenyl-4-acetoxy 71-, 3-ethoxy benzoate (30 g, 0.047 mol), obtained; The solution in step a is dissolved in tetrahydrofuran (300 ml), and 25% aqueous ammonia (60 ml) is added to the mixture. The mixture is then stirred at 50 ° C. for 2 hours and evaporated to dryness under reduced pressure. The remaining crystals recrystallized from a mixture of acetone and water (2: 1, v / v), resulting in the formation of cycloartenyl-3-ethoxy-4-hydroxybenzoate ester (20.5 g), yield 74%, t. square 128-130 ° C.

Specific rotation ССО + 59.5 ° (с 1.00, СНС1Э).

Calculated,%: C 79.27; H 9.89.

C39Hse ° 4 (mol.m. 530.85)

Found,%: C 79.21; H 9.82.

PRI me R 17. Cyclobran L-3-ethoxy-4-hydroxybenzoate.

a) Preparation of cyclobryl-4-acetoxy-3-ethoxybenzoate.

The proposed compound is prepared as described in Example 8a, where 4-acetoxy-3-ethxybenzoic acid (13.9 g, 0.062 mol) and cyclobranol (20.0 g, 0.045 mol) are used instead of 4-ace

153889224

toxi-3-methoxybenzoic acid (13.0 g) and cycloartenol (20.0 g). 23.4 g of cyclobranyl-4-acene are obtained. toxio-3-methoxybenzoate with a yield of 80%, so pl. 161-162 ° C.

Specific rotation + 56.5 ° (with 1.00, CHClj).

Calculated,%: C 77.97; H 9.66. 10 c4-gn & g ° 5 (mol.m. 646.92)

Found,%: C 78.05; H 9.61. b) Preparation of cyclobranyl-3-ethoxy-4-hydroxybenzoate.

Cyclobranyl-4-acetoxy-3-ethoxy-15 benzoate (30 g, 0.046 mol) obtained in step a is dissolved in tetrahydrofuran (300 ml) and 25% aqueous ammonia (60 ml) is added to the resulting mixture. ). After stirring 20 at 50 ° C for 3 hours, the mixture is evaporated to dryness under reduced pressure, and the crystals of the residue are recrystallized from a mixture of acetone and water (2: 1, v / v), resulting in 25 of which receive cycloartenyl-3-ethoxy-4 -oxybenzoate (20.8 g), with a yield of 74%, so pl. 175-176 C.

Specific rotation + 57.5 y (from 1.00, СНС13)

30 Calculated,%: C 79.42; H 10.00. С4.оН60 ° 4 (mom.m. 604.88)

Found,%: C H 10.12.

Example 18. Cyclobranyl-3-ethoxy-4-hydroxycinnamate.

a) Preparation of cyclobryl-4-acetoxy-3-ethoxycinnamate.

To 4-acetoxy-3-ethoxycinnamic acid (27.0 g, 0.108 mol) suspended in 200 ml of toluene, thionyl chloride (16.3 ml, 3 eq.) Is added and stirred at 60 ° C for 2 h. Then the mixture is evaporated under reduced pressure, and the residue is suspended in toluene (150 ml) and pyridine (30 ml). Cyclobranol is added to the suspension, and the mixture is stirred at 60 ° C for 2 hours. After completion of the reaction, the mixture is evaporated to dryness under reduced pressure, and the residue is extracted with 300 ml of chloroform. The extract obtained is washed, dried and evaporated to dryness under reduced pressure. The remaining crystals are recrystallized from ethanol, as a result of which cyclobranyl-4-acetoxy-3-ethoxycinnamate (43.1 g) is obtained, yield 85%, mp 153-154 ° C.

45

to

25153S892

Specific rotation + 37.0 (with 1.00, СНС1,).

Calculated,%: C 78.38; H 9.48.

С4знбг ° 5- (mol-m- 658.93)

Found,%: C 78.44; H 9.43.

b) obtaining cyclobranyl-3-ethoxy-4-hydroxycinnamate.

Cyclobranyl-4-acetoxy-3-ethoxycinnamate (30.9 g, 0.046 mol) obtained in step a is dissolved in 300 ml of tetrahydrofuran, then 25% aqueous ammonia (60 ml) is added. The mixture is stirred at 50 C for 2 hours. After completion of the reaction, the mixture is evaporated to dryness under reduced pressure, and the remaining crystals are recrystallized from a mixture of acetone and water (2: 1, v / v), giving 22.8 g of cyclobranyl-3-ethoxy-4 - hydroxycinnamate (78% yield), m.p. 181-182 ° C.

Specific rotation + 38.0 ° (with 1.00, SNSC).

Calculated,%: C 79.95; H 9.91.

C4HH6204 (mol.m. 630.92)

Found,%: C 79.91; H 9.98.

Example 19 Preparation of cyclo-artenyl-4-hydroxy-3-p-propoxycinate.

The compound was prepared according to Example 18 abb, using cycloartenol, 4-acetoxy-3-p-propoxycinnamic acid, to give cycloartenyl-426

To 4-acetoxy-3-methoxy cinnamic acid (26.5 g, 0.112 mol) suspended in 200 ml of toluene, thionyl chloride (16.3 ml, 3 eq.) Is added and stirred at 60 ° C for 2 hours. The mixture is then evaporated off under reduced pressure, and the residue is suspended in toluene (150 ml) and pyridine (30 ml). Cyclobranol is added to the suspension, and the resulting mixture is stirred for 2 hours. After completion of the reaction, the mixture is evaporated to dryness under reduced pressure, and the residue is extracted with 300 ml of chloroform. The extract obtained is washed, dried and evaporated to dryness under reduced pressure. The remaining crystals are re-crystallized from ethanol, resulting in a cyclobranyl-4-acetoxy-3-methoxycinnamate (44.9 g, yield 91%, mp. 175-176 ° C.

Specific rotation OO +37 25 (with 1.00, CHClj).

Calculated,%: C 78.38; H 9.48. C4 nag05 (mol.m. 658.93) Found,%: C 78.44; H 9.43. b) Preparation of cyclobranyl-4-hydroxy-30 3-methoxycinnamate.

Cyclobranyl-4-acetoxy-3-methoxy cinnammate (44.9 g, 0.068 mol) obtained in step a is dissolved in 900 ml of dioxane and 25% aqueous ammonia is added to this solution.

acetoxy-3-p-propoxycinnamate, which is (90 ml) dropwise. Then the mixture obtained in the amount of 31.0 g (0.046 mol) is stirred at 50 ° C for processing according to the method of example 186, the solution is evaporated for 2 hours to dryness 20.5 g (70%), mp.144-145 ° C.

under reduced pressure. The remaining crystals are washed with ethanol, as a result of which cyclobyl-4-hydroxy-3-methoxycinnamate (40.0 g) is obtained, yield 95.2%, mp. 191-192 ° C.

The specific rotation is oi + 40.2 (s 1.00, СНС13).

Calculated,%: C 79.95; H 9.91.

S4gnbg. ° 4 (mol.m. 630.92)

Found,%: C 79.99; H 9.85.

PRI me R s 20-26. The 24-methylenecycloartanol esters in Examples 20-26 are prepared according to the method previously described for cyclobranols. In these methods, instead of cyclobranolol, the same amount (in moles x) of 24-methylenecycloartanol is used. The outputs, melting points and specific rotations (from 1.00, CHC1) of these compounds are given in Table. one.

40

45

50

under reduced pressure. The remaining crystals are washed with ethanol, as a result of which cyclobyl-4-hydroxy-3-methoxycinnamate (40.0 g) is obtained, yield 95.2%, mp. 191-192 ° C.

Specific rotation + 38.5 (with 0.99, СНС1,). B

Calculated,%: C 79.82; H 9.80.

C4, HU04 (mol.m. 616.89)

Found,%: C 79.77; H 9.83.

IR (KBG) $, cm-: 3500, 2920, 2850, 1690.1 1600, 1510, 1265, 1155.

NDP (CDC1,), Ј: 0.36 (1H, 1/2 AV sq., 4.8 Hz); 0.60 (1H, 1/2 AV sq., 4.8 Hz); 0.68-2.20 (27H, m); 0.89 (6H, s); 0.96 (6H, s); 1.62 (9H, s ;; 3.90 (ZN, s); 4.50-4.90

Example 27. Cyclobranyl-4-guide-55 (1H, m); 5.97 (1H, bhp); 6.27

roxy-3-methoxycinnamate (1H, 1/2 AVsq., 15.6 Hz); 6.75-7.20

a) Preparation of cyclobranyl-4-ace- (3N, m); 7.9 (1H, 1/2 AV sq.,

toxio-3-methoxycinnamate (15.6 Hz).

2

26

To 4-acetoxy-3-methoxy cinnamic acid (26.5 g, 0.112 mol) suspended in 200 ml of toluene, thionyl chloride (16.3 ml, 3 eq.) Is added and stirred at 60 ° C for 2 hours. h. Then the mixture is evaporated under reduced pressure, and the residue is suspended in toluene (150 ml) and pyridine (30 ml). Cyclobranol is added to the suspension, and the resulting mixture is stirred for 2 hours. After completion of the reaction, the mixture is evaporated to dryness under reduced pressure, and the residue is extracted with 300 ml of chloroform. The extract obtained is washed, dried and evaporated to dryness under reduced pressure. The remaining crystals recrystallized from ethanol, resulting in a cyclobranyl-4-acetoxy-3-methoxycinnamate (44.9 g), yield 91%, mp. 175-176 ° C.

Specific rotation OO +37 (with 1.00, CHCl j).

Calculated,%: C 78.38; H 9.48. C4 nag05 (mol.m. 658.93) Found,%: C 78.44; H 9.43. b) Preparation of cyclobranyl-4-hydroxy-3-methoxycinnamate.

Cyclobranyl-4-acetoxy-3-methoxycinnamate (44.9 g, 0.068 mol) obtained in step a is dissolved in 900 ml of dioxane and 25% aqueous ammonia is added to this solution.

(90 ml) dropwise. The mixture is then stirred at 50 ° C. for 2 hours and the solution is evaporated to dryness.

under reduced pressure. The remaining crystals are washed with ethanol, as a result of which cyclobyl-4-hydroxy-3-methoxycinnamate (40.0 g) is obtained, yield 95.2%, mp. 191-192 ° C.

Specific rotation + 38.5 (with 0.99, СНС1,). B

Calculated,%: C 79.82; H 9.80.

C4, HU04 (mol.m. 616.89)

Found,%: C 79.77; H 9.83.

IR (KBG) $, cm-: 3500, 2920, 2850, 1690.1 1600, 1510, 1265, 1155.

NDP (CDC1,), Ј: 0.36 (1H, 1/2 AV sq., 4.8 Hz); 0.60 (1H, 1/2 AV sq., 4.8 Hz); 0.68-2.20 (27H, m); 0.89 (6H, s); 0.96 (6H, s); 1.62 (9H, s ;; 3.90 (ZN, s); 4.50-4.90

(1H, m); 5.97 (1H, bhp); 6.27

2715

PRI me R 28. Cycloartelic sulphate of 4-hydroxy-3-methoxy-o-methylcinnamic acid.

. a) Preparation of cycloartenyl ester of 3-methoxy-4-propionyloxy-0Ј-methylcinnamic acid.

Thionyl chloride (40.0 ml, 2 eq.), Toluene (400 ml) and dimethylformamide (0.5 ml) are added to 3-methoxy-4-propionchghoxy-oЈ-methylcinnamic acid (72.0 g, 0.272 mol). ), and semi-. The mixture was stirred for 1.5 hours. After concentration under reduced pressure, dioxane (100 ml) was added to the mixture and stirred at OC. Cycloartenol (80.0 g, 0.187 mol) dissolved in pyridine (300 ml) is added to this mixture and stirred at 60 ° C for 3 hours. The reaction mixture is evaporated under reduced pressure and the residue is dissolved in chloroform (800 ml ). The resulting solution was washed with saturated aqueous NaHCO, and the aqueous layer was extracted with chloroform (500 ml x 2). The combined chloroform layers are dried and evaporated under reduced pressure, and the residue is purified on a chromatographic column with silica gel (solvent – gay dan: methylene chloride 5:19 volume / volume), resulting in a 3-methoxy-4-cycloarbonyl ester propionyloxy-methylchloric acid (110 g), yield 87.1%, mp. 130-131 ° C.

Specific rotation ° 0 + 41.4 ° (with 1.00, СНС13).

Calculated,%: C 78.53; H 9.59.

 (mol.m. 672.9)

Found,%: C 78.59; H 9S52.

IR (KVGI,: 2920., 2850, 1765, 1710, 1630, -1600, 1510, 1240, 1140, 1110.

PMR (CDC1,), S: 0.39 (1H, 1/2 AV sq., 4.2 Hz); 0.60 (1H, 1 / 2ABB 4.2 Hz); 0.60-2.20 (27H, m); 0.90

(6H, s); 0.98 (6H, s); 1.27 (MN, t,

7.2 Hz); 1.58 (ZN, sh. S), 1.68 (ZN ,,.

bc, 2.12 (3N, d, 1.2 Hz); 2.62

(2H, q, 7.2 Hz); 3.80 (AH, s);

4.50-5.30 (2H, m); 6.80-7.70 (4H, m)

b) Preparation of cycloartenyl ester of 4-hydroxy-3-methoxy-methyl cinnamic acid (cycloartenyl ester-ib-methyl feruric acid). .

five

0

92

five

0

five

0

five

0

five

28

To the cycloartenyl ester of 3-methoxy-4-propionyloxy-α-methylcinnamic acid (84.0 g, 0.125 mol) obtained in stage a, dissolved in dioxane (1000 ml), is added 25% aqueous ammonia (200 ml) , and the resulting solution was stirred at 50 ° C for 2 hours. The reaction mixture was then concentrated under reduced pressure to remove the solvent, and the residue was dissolved in chloroform. The resulting chloroform solution is washed with saturated brine (500 ml), and the aqueous layer is extracted with chloroform (300 ml x 2), the combined chloroform layers are dried, concentrated under reduced pressure, and the residue is recrystallized from a mixture of methylene chloride and methanol (1: 4, volume / vol), resulting in a cycloartenyl ester of 4-hydroxy-3-methoxy-about-methylcinnamic acid (73s, 0 g), yield 94.8%, m.p. 143-144 ° C.

Specific rotation “О + 44.1 ° (с 1.00, СНС13). i Calculated,%: C 79.82; H 9.80.

C41 (mol. M. 616.93)

Found,%: € 79.88; H 9.81.

IR (KvgN, 3400, 2900, 2850, 1695, 1690, 1625, 1600, 1510, 1250, 1110.

PMR (CDC14), S: 0.38 (1H, 1/2 AV sq., 4.2 Hz); 0.59 (1H, 1/2 AV sq., 4.2 Hz); 0.60-2.30 (27H, m); 0.88 (6H, s); 0.97 (6H, s); 1.60 (ZN, ws); 1.66 (ZN, bhp); 2.12 (3N, d, 1.2 Hz); 3.88 (ЗН, s); 4.50-5.30 (2H, m); 5.80 (1H, bhp); 6.70-7.70 (4H, m).

Approx. 29. 4-Hydroxy-3-methoxy-? -Methylcinnamic acid cyclic branyl sulphate.

a) Preparation of cyclobranyl ester of 3-methoxy-4-propionyloxy-c-methyl cinnamic acid.

To 3-methoxy-4-propionyloxy -, - methylcinnamic acid (15.59 g, 0S059 mol) suspended in 50 ml of toluene, 50 ml of thionyl chloride (20 ml, 4.5 eq.) And di methylformamicum ( 5 drops), and the resulting mixture was stirred at 60 ° C for 2 hours. Then the solvent was distilled off under reduced pressure. The residue is suspended in 150 ml of toluene and 30 ml of anhydrous lipiddine, and

291538892

cyclobranol (20 g, 0.045 mol) is added to this suspension. The resulting mixture is stirred at 60 ° C for 2 hours, then concentrated under reduced pressure. The residue is extracted with chloroform (300 ml), and the chloroform solution is washed, dried and evaporated to dryness under reduced pressure. The crystalline residue is washed with ethanol JQ (50 ml) and recrystallized from a mixture of acetone and water (19: 1, v / v), resulting in the preparation of cycloranyl ester 3-methoxy-4-propionyloxy-o-methyl-5-tric acid (24 , 69 g), yield 79.2%, so pl. 146-147 ° C.

Specific rotation + 39.2 °

thirty

35

(from 1.00, СНС13).

Calculated,%: C 78.67; H 9.68. 20

C45H ". ° 5- (mol.m. 686.98)

Found,%: C 78.75; H 9.62.

IR (KBG)}, cm 1: 3400, 2950,. 2850, 1760, 1710, 1630, 1600, 1240, 1150, 1120.25

HMR (CDC14) 8: 0.37 (1H, 1/2 AV sq., 4.8 Hz); 0.62 (1H, 1/2 AV sq., 4.8 Hz); 0.70-2.22 (27H, m); 0.92 (6H, s); 0.99 (6H, s); 1.29 (ЗН, t, 7.2 Hz); 1.64 (9H, s), 2.14 30 (3N, d, 1.2 Hz); 2.63 (2H, q, 7.2 Hz); 3.84 (ЗН, s); 4.84-4.88 (1H, m); 6.80-7.08 (ЗН, m); 7.59 (1H, q, 1.2 Hz).

b) Preparation of 4-hydroxy-3-methoxy-cЈ-methylcinnamic acid cycloranilic ester.

The 3-methoxy-4-propionyloxy-methyl methyl-boric acid cyclobranilic ester (24.69 g, 0.036 mol) obtained in step a is dissolved in 400 ml of dioxane, and a 25% aqueous solution is added to the solution obtained. ammonia is added dropwise. The resulting mixture is stirred at 50 ° C for 2 hours, and then the solvent is removed by distillation under reduced pressure. The crystalline residue is washed with ethanol and recrystallized from a mixture of acetone and water (19: 1, v / v), as a result of which a cyclobranyl ester of 4-hydroxy-3-methoxy-oЈ-metric curric acid is obtained (21.72 g), yield 95%

m.p. 185-186 ° C.

i go

40,

45

Found,%: C 79.90; H 9.98.

IR (KBV), cm-: 3380, 2920, 2850, 1693, 1600, 1510, 1285, 1250, 1120.

PMR (CDC13), Ј: 0.36 (1H, 1 / 2AB Aq, 4.8 Hz); 0.61 (1H, 1/2 AV sq., 4.8 Hz); 0.76-2.30 (27H, m), 0.91 (6H, s); 0.99 (6H, s); 1.63 (9H, s); 2.14 (3N, d, 1.2 Hz); 3.90 (ЗН, s); 4.48-4.84 (1H, m); 5.84 (1H, bhp); 6.80-6.98 (ЗН, m); 7.55 (1H, 0q, 1.2 Hz).

PRI me R 30. 24-Methylencyclo-artanyl ester of 4-hydroxy-3-labels-C.K-L-methylcinnamic acid.

a) Preparation of 3-methoxy-4-propionyloxy-methylcinnamic acid 24-methylenecyclo-articanyl ester.

To 3-methoxy-4-propionyloxy-o-methylcinnamic acid (0.8 g, 0.003 mol) suspended in 2 ml of toluene, thionyl chloride (0.5 ml, 2.2 eq.) And 2 drops of dimethyl formamide are added. and the mixture was stirred at 60 ° C for 2 hours. Then the solvent was distilled off under reduced pressure. The residue was suspended in toluene (2 ml) and anhydrous pyridine (1 ml), and 24-methylenecycloartanyl (1 g, 0.0023 mol) was added to the resulting suspension. The resulting mixture was stirred at 60 ° C for 2 hours, and then the solvent was distilled off under reduced pressure. The resulting residue is extracted with chloroform 20 ml, and the chloroform extract is washed with sodium bicarbonate, dried and evaporated under reduced pressure. The crystalline residue is washed with ethanol (5 ml) and recrystallized from a mixture of acetone and methanol (1: 1, volume / volume), resulting in a 24-methylenecyclo-arthanyl ester of 3-methoxy-4-propionyloxy-methylcoric acids (1.35 g), yield 86.6, m.p. 134-135 ° C.

The specific rotation is about + 41.2 ° (with 1.00, СНС13). at

Calculated,%: C 78.67; H 9.68.

C46Hfefe ° s (mol.m. 686.98)

Specific rotation (from 1.00, СНС1Calculated,%: С 79.95; H 9.91. C4iH6204 (mol. 630.92)

Found,%: C 78.75; H 9.62.

IR (KBV) 0, cm-H 3400, 2920, T ° + 43.7 ° 55 2850, 1760, 1240, 1115.

PMR (CDC14), S: 0.36 (1H, 1 / 2AB Apt, 4.2 Hz); 0.61 (1H, 1/2 AV sq., 4.2 Hz); 0.70-2.22 (34H, m); 0.88

thirty

Q 5

five

0

five

0

0

0,

five

Found,%: C 79.90; H 9.98.

IR (KBV), cm-: 3380, 2920, 2850, 1693, 1600, 1510, 1285, 1250, 1120.

PMR (CDC13), Ј: 0.36 (1H, 1 / 2AB Aq, 4.8 Hz); 0.61 (1H, 1/2 AV sq., 4.8 Hz); 0.76-2.30 (27H, m), 0.91 (6H, s); 0.99 (6H, s); 1.63 (9H, s); 2.14 (3N, d, 1.2 Hz); 3.90 (ЗН, s); 4.48-4.84 (1H, m); 5.84 (1H, bhp); 6.80-6.98 (ЗН, m); 7.55 (1H, 0q, 1.2 Hz).

PRI me R 30. 24-Methylencyclo-artanyl ester of 4-hydroxy-3-labels-C.K-L-methylcinnamic acid.

a) Preparation of 3-methoxy-4-propionyloxy-methylcinnamic acid 24-methylenecyclo-articanyl ester.

To 3-methoxy-4-propionyloxy-o-methylcinnamic acid (0.8 g, 0.003 mol) suspended in 2 ml of toluene, thionyl chloride (0.5 ml, 2.2 eq.) And 2 drops of dimethyl formamide are added. and the mixture was stirred at 60 ° C for 2 hours. Then the solvent was distilled off under reduced pressure. The residue was suspended in toluene (2 ml) and anhydrous pyridine (1 ml), and 24-methylenecycloartanyl (1 g, 0.0023 mol) was added to the resulting suspension. The resulting mixture was stirred at 60 ° C for 2 hours, and then the solvent was distilled off under reduced pressure. The resulting residue is extracted with chloroform 20 ml, and the chloroform extract is washed with sodium bicarbonate, dried and evaporated under reduced pressure. The crystalline residue is washed with ethanol (5 ml) and recrystallized from a mixture of acetone and methanol (1: 1, volume / volume), resulting in a 24-methylenecyclo-arthanyl ester of 3-methoxy-4-propionyloxy-methylcoric acids (1.35 g), yield 86.6, m.p. 134-135 ° C.

The specific rotation is about + 41.2 ° (with 1.00, СНС13). at

Calculated,%: C 78.67; H 9.68.

C46Hfefe ° s (mol.m. 686.98)

Found,%: C 78.75; H 9.62.

311

(6H, s); 0.96 (6H, s); 1.26 (3N, m, 7.2 Hz); 2.11 (3N, d, 1.2 Hz); 2.60 (2H, q, 7.2 Hz); 3.80 (ЗН, s); 4.44-4.86 (1HS m); 4.86-5.26 (2H, m 6.76-7.08 (ЗН, m); 7.55 (1H, sq., 1.2 Hz).

b) Preparation of 24-methylenecycloartyl 4-hydroxy-3-me-toxy-o-methylcinnamic acid ester.

24-Methylencycloartanyl 3-methoxy-4-propionyloxy, methylchloric acid ester (1.35 g, 0.002 mol) obtained in step a is dissolved with HF dioxane (20 ml) and 25% waxy is added to this solution ammonia (2 ml) is added dropwise. The resulting mixture is stirred at 50 ° C for 2 hours, then the solvent is distilled off under reduced pressure. The crystalline residue is washed with ethanol and recrystallized from ethanol, whereby 4-hydroxy-3-methoxy-4-24-methylenecycloartanyl ester is obtained; methylcinnamic acid (1.02 g) is obtained, yield 82.2%, mp. 144145 s g 41

Specific rotation I J (with 1.00, СНС13).

Calculated,%: C 79B95; H 9.91

D

44,8e

C43n & G. ° 4 (mol.m. 630.92)

Found,%: C 79.99; H 9.84.

IR (KBG) $, cm- (:: 3400., 2900, 2850, 1690, 1600, 1510, 1250, 1110.

PMR (CDC13) B: 0.37 (1H, 1/2 AB apt., 4.2 Hz); 0.61 (1H 1 / 2ABB 4.2 Hz); 0.70-2.21 (34H, m); 0.89 (6H, s); 0.98 (6H, s), 2.14 (3N, d, 1.2 Hz); 3.88 (ЗН, s); 4.50-4.88 (1H, m); 4.88-5.28 (2H} m); 5980 (1H, s.s.); 6.82-7.10 (ЗН5 m), 7.59 (1H, q, 1.2 Hz).

Example 31. 4-Hydroxy-3-methoxy-t (-Cl3-1N-hydrochloric acid) cycloartenyl ester.

a) Preparation of 4-butyryloxy-3-methoxy-4--ethyl cinnamic acid cycloartenyl ester.

Thionyl chloride (15.0 ml, 3.3 eq.) Was added dropwise to a solution of 4-butyryloxy-3-methoxy-oЈ-ethyl-cinnamic acid (18.0 g, 0.062 mol) in benzene (40 ml) with 0 ° C, and the resulting mixture is heated to 60 ° C and left under stirring for 2 hours. Then, the excess thionyl chloride, the solvent is removed by distillation under reduced pressure. 10 ml of pyridine and 40 ml of dioxane added

32

Yut to the residue. While the mixture was cooled at 0 ° C, a solution of cycloartenol (17.5 g, 0.041 mol) in pyridine (30 ml) was added dropwise to it. This reaction mixture is left under stirring at 20 ° C. The solvent is then distilled off under distillation under reduced pressure. The residue was extracted with chloroform (200 ml) and the extract obtained was concentrated in vacuo. The residue is recrystallized from a mixture of acetone and methanol (1: 1, v / v), as a result of which 4-butyryloxy-3-methoxy-ethyl-boric acid cycloartenyl ester (22.4 g) is obtained, yield 77.9%, m.p. 118.5-119.5 ° C.

Specific rotation + 35.7 ° 0 (s, 1.00, СНС1,).

Calculated,%: C 78.81; H 9.78.

C44n & ° 5 (mol.m. 701.00) p Found,%: C 78.72; H 9.86.

IR (KBG)} cm (: 3400, 2920, 280Q, 5 1700, 1600, 1510, 1230, 1120.

PMR (CDC1), S: 0.36 (1H, 1 / 2AB ap., 4.2 Hz); 0.52-2.26 (29H, m); 0.61 (1H, 1/2 AV sq., 4.2 Hz); 0.90 (6H, s); 0.96 (6H, s); 1.04 (ZN, t, 0 7.2 Hz); 1.18 (ЗН, t, 7.2 Hz); 1.60 (3N, s); 1.66 (3N, s); 2.26-2.82 (4H, m); 3.79 (ЗН, s); 4.50-4.88 (1H, m); 4.88-5.28 1H, m); 6.70-7.12 (GH, m); 7.48-7.68 (1H, m).

b) Preparation of 4-hydroxy-3-methoxy-ethylcinnamic acid cycloartenyl ester.

The 4-butyryloxy-3-methoxy-o-ethylcyclic acid cycloartenyl ester (22.0 g, 0.0314 mol) obtained in step a is dissolved in dioxane (200 ml) and 25% is added to the resulting solution. aqueous ammonia (20 ml) dropwise. Prep 5

0

The mixture is heated at 50 ° C.

5 hours. Then the solvent is removed by distillation under reduced pressure. The residue is extracted with chloroform (200 ml) and the extract is concentrated in vacuo. The residue is recrystallized from a mixture of acetone and methanol (1: 1, v / v), as a result of which 4-oxo-3-methoxy-c4-ethyl cyclic acid cycloartenyl ester is obtained (17.2 g), yield 86.8% , t.p.136- 137 S.

Specific rotation ci + 41,5 °

(from 1.00, СНС15).

D

331

Calculated,%: C 79.95; H 9.96.

C ".H62. ° 4 (mol.m. 630.92)

Found,%: C 79.90; H 9.83.

IR (KVgN, see 1: 3400, 2830, 1700, 1595, 1510, 1240, 1120.

Poland (CDC1,), S: 0.35 (1H, 1/2 AB q 4.2 Hz); 0.50-2.18 (27H, m); 0.60 (1H, 1/2 AV sq., 4.2 Hz); 0.89 (6H, s); 0.95 (6H "s), 1.19 (ZN, t, 7.2 Hz); 1.57 (ZN, s); 1.65 (ЗН, с) 2.56 (2Н, ш, с, кв., 7.2 Hz), 3.87 (ЗН, с); 4.47-4.85 (1H, m); 4.85-5.24 (1H, m), 5.76 (1H, msec); 6.96-7.09 (GH, m); 7.24-7.64 (1H, m).

. Approx 32. 4-hydroxy-5b-methylcinnamic acid cycloartenyl ester.

a) Preparation of cycloartenyl 4-propionyloxy-methylcinnamic ester.

Thionyl chloride (18.1 ml, 3.3 eq.) And dimethylformamide (0.5 ml) are added dropwise to a solution of 4-propionyloxy-methylcinnamic acid.

(17.6 g, 0.075 mol) in benzene (40 ml) at 0 ° C. The resulting mixture is heated to 60 ° C and left under stirring for 2 hours. Then, excess thionyl chloride is removed and the solvent is removed by distillation under reduced pressure. 40 ml of dioxane and 10 ml of pyridine are added to the residue. While the mixture was cooled at 04 ° C, a solution of cycloartenol (21.3 g, 0.050 mol) in pyridine (40 ml) was added dropwise. The reaction mixture is heated to 20 ° C and left under stirring overnight. Then the solvent was distilled under reduced pressure, and the residue was extracted with chloroform (200 ml). The extract obtained is concentrated under reduced pressure, and the residue is recrystallized from a mixture of acetone and ethanol (1: 2, volume / volume), and the result is a 4-propionyl-hydroxy-methyl-cyclic acid cycloartenyl ester (27.0 g) yield 38.9%, so pl. 87-88 ° C.

The specific rotation is 45.9 (with 1.00, СНС1,).

Calculated,%: C, 80.33; H 9.72.

° 4 (mol. 642.93)

Found,%: C 80.31; H 9.79.

IR (KBV) $, cm 1: 3400, 2920, 2850, 1760, 1700, 1260, 1215, 1115,

Poland (CDC13), &: 0.36 (1H, 1 / 2AB, 4.2 Hz); 0.52-2.20 (27H, m); 0.61 (1H, 1/2 AV sq., 4.2 Hz); 0.89

34

0

(6H, s), 0.97 6H, s); 1.25 (3N, t, 7.2 Hz); 1.57 (ZN, s); 1.65 (3N, s); 2.10 (3N, d, 1.2 Hz); 2.58 (2H, aq., 7.2 Hz); 4.28-4.84 (1H, m);

4.92-5.24 (1H, m); 6.92-7.09 (2H, m); 7.11-7.50 (2H, m); 7.50-7.70 (1H, m).

b) Preparation of cycloartenyl 4-hydroxy-methylcinnamic ester.

The 4-propionyloxy-aЈ-methylcinnamic acid cycloartenyl ester (27.0 g, 0.042 mol) obtained in step a is dissolved in dioxane 5 (200 ml), and 25% aqueous ammonia is added to this solution. The mixture is heated to 50 ° C and left under stirring for 2 hours. Then the solvent is distilled off under reduced pressure, the residue is extracted with chloroform (200 ml). The extract obtained is concentrated in vacuo, and the residue is recrystallized from ethanol, resulting in 4-hydroxy-0Ј-methylcinnamic acid cycloartenyl ester (20.5 g), yield (83.1%), mp. 190-191 0.

The specific rotation is 31 + 45.8 (with 1.00, СНС1).

Calculated,%: C 81.86; H 9.96.

C HsfcO, (mol.m. 586.86)

0

five

0

0

five

0

five

Found,%; C, 81.77; H 9.99.

, one

IR (KBV) W, cm-1: 3400, 2992, 5 2985, 1700, 1675, 1600, 1510, 1260,

1200, 1170.

NDP (CDC13), Ј: 0.36 (1H, 1/2 AV sq., 4.2 Hz); 0.52-2.24 (27H, m); 0.61 (1H, 1/2 AV sq., 4.2 Hz); 0.90 (6H, s); 0.98 (6H, s); 1.61 (ZN, s); 1.64 (ZN, s); 2.13 (3N, d, 1.2 Hz); 4.50-4.88 1H, m); 4-85-5.24 (1H, m); 5.88-6.60 (1H, m); 6.68-7.12 (2H, m); 7.12-7.50 (1H, m); 7.50-7.68 (1H, m).

PRI me R 33. 24-Methylencyclo-artanyl ester of 4-hydroxy-y-methyl-boric acid.

a) Preparation of 4-propionyl-hydroxy-methylcinnamic acid 24-methylenecycloarthenyl ester.

Thionyl chloride (18.1 ml, 3.3 eq.) And dimethylformamide (0.5 ml) are added dropwise to a solution of 4-propionyloxy c-methylcinnamic acid (17.6 g, 0.075 mol) in benzene ( 40 ml) at GeS. The resulting mixture is heated to and continued to stir for 2 hours. Then an excess of thionyl chloride and the solvent is distilled off at 3515.

lower pressure. 20 ml of dioxane and 40 ml of pyridine are added to the residue. While the mixture was cooled, 24-methylenecycloartanol (0.050 mol) was added, and the mixture was heated to 20 ° C and continued to stir overnight. The solvent is then removed by distillation in vacuo, and the resulting residue is extracted with 200 ml of chloroform. The extract obtained is concentrated under reduced pressure, and the residue is recrystallized from a mixture of acetone and methanol (1: 1, v / v), as a result of which 24-methylene cycloartanyl 4-propionyloxy-o-methylcinnamic acid ester is obtained. (25.8 g), yield 78.5%, mp. 94-95 ° C

Specific rotation 1 + 34.7 ° (with 1.00, СНС1,).

Calculated,%: C, 80.44; H 9.82.

C44.H64 ° 4 (mol.m. 656.95)

Found,%: C 80.39; H 9.78.

b) Preparation of 24-methylenecyclo-articanyl 4-hydroxy-oЈ-methylcinnamic ester.

24-Methylencycloartanyl ester of 4-propionyloxy-methyl methyl acid (24.0 g, 0.036 mol) obtained in step a is dissolved in dioxane (200 ml), and 25% aqueous ammonia is added to the resulting solution droplets. The resulting mixture is heated under and continue to stir for 2 hours. Then the solvent is removed by distillation under reduced pressure, and the residue is extracted with chloroform (200 ml). The extract obtained is concentrated in vacuo, and the residue is recrystallized from a mixture of acetone and methanol (1: 1, v / v) to give 24-methylenecycloartanyl 4-hydroxy-ко-methylcinnamic acid ester (19.4 g), yield 89, 6%, mp. 195 196 ° C.

Specific rotation of Z-9 + 43.8 ° (with 1.00, СНС13).

Calculated,%: C 81.95; H 10.07. C41bo ° W (mol.m. 600.89) Found,%: C 81.90; H 10.14, Example 34. 4-hydroxy-b-ethyl cinnamic acid cycloartenyl ester. ,,

a) Preparation of cycloartenyl 4-butyryl hydroxy-o6-ethyl cinnamic acid ester.

0

five

about 5 5

0 5

0

36

Thionyl chloride (4.8 ml, 5 eq.) Was added dropwise to a solution of 4-butyryloxy-ethyl boric acid (3.5 g, 0.0133 mol) in benzene (7 ml) at. The resulting mixture is heated to 60 ° C and continue to stir for 2 hours. Then, from -. the thionyl chloride excess is removed by distillation under reduced pressure. After adding 10 ml of pyridine to the residue, a solution of cycloartenol (2.85 g, 0.0067 mol) in 10 ml of pyridine was added dropwise at 0 ° C to the mixture. The mixture is heated to 20 ° C and continue to stir overnight. The solvent was then removed by distillation under reduced pressure, and the residue was extracted with 40 ml of chloroform. The extract obtained is concentrated in vacuo, and the residue is recrystallized from a mixture of acetone and ethanol (1: 1, v / v), resulting in the preparation of 4-butyryloxy-o-ethylchloric acid cycloartenyl ester (3,63 g), yield 80.7%; mp. 88-89 ° S.go

Specific rotation L + 41.2 ° (with 1.00, СНС13).

Calculated 80.55; H 9.92.

S45nb ° 4 (mol.m. 670-98)

Found,%: C 80.64; H 9.84.

b) Preparation of the cycloartenyl ester of 4-hydroxy-eЈ,-ethyl boric acid.

The 4-butyryloxy-cЈ-ethylcyclic acid cycloartenyl ester (2.00 g, 0., 003 mol) obtained in step a is dissolved in dioxane (20 ml), and 25% aqueous ammonia is added to the resulting solution (2 ml) is added dropwise. The mixture is then heated to 50 ° C and stirring is continued for 5 hours. The solvent is removed by distillation under reduced pressure, and the residue is extracted with chloroform (20 ml). The extract obtained is concentrated in vacuo, and the residue is recrystallized from acetone, as a result of which 4-oxo-ethyl cyclic acid cycloartenyl ester (1.68 g) is obtained, yield 93.2%, mp. 162-163 ° C.

Specific rotation of 46,1 ° (from 1.00, СНС13).

Calculated,%: C 81.95; H 10.07. C-IN60 ° (mol.m. 600.89) Found,%: C 81.88; H 10.12.

37 .-.

IR (KBrH, 3300, 2920, 2800, 1760, 1710, 1625, 1500, 1280, 1240, 1165, 1120.

Poland (CDC13), S: 0.36 (1H, 1/2 AB q4.2.2 Hz); 0.52-2.22 (27H, m); 0.61 (1H, 1/2 AV sq., 4.2 Hz); 0.90 (6H, s); 0.96 (6H, s); 1.19 (ZN, t, 7.2 Hz); 1.60 (3N, s); 1.67 (3N, s) 2.57 (1H, q, 7.2 Hz); 4.47-4.88 (1H, m); 4.92-5.32 (1H, m); 6.43-6.77 (1H, m); 6.68-7.04 (2H, m); 7.12-7.48 (2H, m); 7.52-7.69 (1H, m)

PRI me R 35. Preparation of 3-ethoxy-4-hydroxy-methylcinnamic acid cyclopranyl ester.

The indicated compound was prepared according to Example 316, however, the 3-ethoxy-4-propionyloxy, cyclic-ethylnyl ester, y-methylcinnamic acid (21.7 g, 0.031 mol) was used as the starting compound, yield was 16.1 g (80, 5%), mp. 174-175 ° C.

Specific rotation g ° + 42.4 ° (with 1.00, СНС13).

Calculated,%: C 80.07; H 10.00.

 (mol.m. 644.94)

Found,%: C 80.18; H 10.05.

Example 36. Preparation of 3-ethoxy-4-hydroxy-propylcinnamic acid cyclo-artenyl ester.

The indicated compound was prepared according to Example 316, however, 3-ethoxy-4-valeryloxy-oЈ-propylcinnamic acid cyclo-artenyl ester was used as a starting material, yield 16.8 g (72.8%), t.p. 111 112 ° C.

Specific rotation + 40.7 °

one

(from 1.00, СНС1,).

Calculated,%: C, 80.19; H 10.10.

CHN & 6 ° + (mol.m. 658.97)

Found,%: C 80.26; H 10.02.

PRI me R 37. Preparation of 3-ethoxy-4-hydroxy-oЈ-propylcinnamic acid cyclopranyl ester.

The indicated compound was prepared according to Example 316; however, as the starting material, 3-ethoxy-4-valeryloxy-propyl diconic acid cyclobranyl ester (24.2 g, 0.032 mol) was used, yield 16.7 g (72.8%) m.p. 134 ° C135 ° C.

Specific rotation oOr + 37.1 ° (with 1.00, СНС1}).

Calculated,%: C 80.31; H 10.18.

C45N6J04 (mol.m. 672.99)

., .

ten

3889238

Found,%: C, 80.25; H 10.24

PRI me R 38. Preparation of 3-ethoxy-4-hydroxy-o-butyl butanoic acid cyclo-artenyl ester.

The above compound was prepared according to Example 316, however, 4-capryloxy-3-ethoxy-about-butyl boric acid cycloartenyl ester was used as a starting material, yield 16.2 g (80.2%), mp. 99-100 ° C.

The specific rotation is oij + 40.0 ° (c 1.00, СНС1,).

Calculated,%: C 80.31; H 10.18.

C45Nbe04 (mol.m. 672.99)

Found,%: C 80.21; H 10.22.

PRI me R 39. Preparation of 4-hydroxy-2Q 3-propoxy o-methylcinnamic acid cyclo-artenyl ester.

This compound was prepared according to Example 316; however, 4-pro-25 pionyloxy-3-propoxy-methylcinnamic acid cycloartenyl ester (23.1 g, 0.033 mol) was used as a starting material (23.1 g, 0.033 mol); (80.8%), so pl. 138-139 ° C ..

Specific rotation + 43.7y (with 1.00,).

Calculated,%: C 80.07; H 10.00.

15

thirty

C43H6404 (mol.m. 644.94)

35

40

45

Found,%: C 80.19; H 10.04.

EXAMPLE 40. Preparation of 4-hydroxy-3-butoxy-o-methylcinnamic acid cyclo-artenyl ester.

The above compound was prepared according to Example 316, however, 4-gropylopionyloxy-3-butoxy-methyl cyclic acid cycloartenyl ester (22.9 g, 0.032 mol) was used as the starting compound (yield, 16.5 g (78%), m.p. 126-ShaS.

Specific rotation G 1 + 39.7 ° (with 1.00, CHCL,).

Calculated,%: C, 80.19; H 10.10.

C44H66 ° 4 (mol.m. 658.97)

Found,%: C 80.24; H 10.03.

Example 4: 24-Methylencyclo-artanyl ester of 4-hydroxy-3-methoxy-oЈ-ethyl cinnamic acid.

a) Preparation of 4-butyryl-3-methoxy-o-ethyl-ethyl-boric acid 24-methylenecyclo-artanyl ester.

Thionyl chloride (15.0 ml, 3.3 eq.) 55 is added dropwise to a solution of 4-butyryloxy-3-methoxy-o-ethyl-cinnamic acid (18.0 g, 0.062 mol) in 40 ml of benzene at 0 ° C and then 50

39

The resulting mixture is heated for 2 hours. Then an excess of tinil chloride and the solvent is removed by distillation under reduced pressure. 40 ml of pyridine and 40 ml of dioxane are added to the residue. While the mixture was cooled at OC, 24-methylene cycloartanol (18.1 g, 0.041 mol) was added, and then the resulting mixture was heated to 20 ° C and left under stirring overnight. The solvent was distilled off under reduced pressure, and the residue was extracted with chloroform (200 ml). The extract obtained is concentrated in vacuo, and the residue is recrystallized from a mixture of acetone and ethanol (1: 1, v / v), resulting in a 24-methylene cycloartanyl ester of 4-butyryloxy-3-methoxy-b-ethyl boric acid. (22.8 g), yield 77 „8%, so pl. 127-128 ° C.

Specific rotation tOj, + 33 s 7 ° (s 1.00, СНС1,).

Calculated,%: C 78.94; H 9587. SD7H70Og (mol.m. 715.03) Found;%: C 78.89; H 9.88. IR (KBG)), cm-: 3400, 2920, 2850, 1760, 1710, 1625, 1510, 1230, 1120.

Poland (CDCl3), Ss 0.36, (1H, 1/2 AB ap., 4.8 Hz); 0.52-2.22 (29H, m); 0.61 (1H, 1/2 AV sq., 4.8 Hz); 0.92 (6H, s); 0.97 (6H, s); 1.03 (3N, t, 7.2 Hz); 1.18 (ЗН, t, 7.2 Hz); 1.60 (9H, s); 2.22-2.82 (4H, m); 3.81 (ЗН, s); 4.48-4.90 1H, m); 6.70-7.18 (ЗН, m); 7.40-7.64 (1H, m). b) Preparation of 24-methylenecycloarthenyl 4-hydroxy-3-methoxy-o-6-ethylcinnamic ester

The 4-butyryloxy-3-methoxy-ethylchloric acid 24-methylencyclo-artachyl ester (21.5 g, 0.0301 mol) obtained in a stage ae is dissolved in dioxane (200 ml) and aqueous ammonia (20 ml) is added to the resulting solution ml) dropwise. The mixture is heated to 50 ° C and stirred for 5 hours. Then the solvent is distilled off under reduced pressure, and the residue is extracted with chloroform (200 ml). The resulting extract is concentrated in vacuo, and the residue is recrystallized from ethanol. to provide the 4-hydroxy-2-methoxy-t 24-methylenecycloartanyl ester etilko153889240

Acidic acid (17.3 g), yield 89.1%, mp. 137-138 ° C.

Specific rotation “Wow + 37.7 ° 5 (from 1.00, СНС1Э).

Calculated,%: C 80.07; H 10.00. (mol.m. 644.94)

Found,%: C 80.13; H 10.12.

IR (KBG), 3400, 2930, U 1696, 1235, 1130.

PMR (CDC13), &: 0-, 38 (1H, 1 / 2AVB 4.8 Hz); 0.52-2.22 (27H, m)} 0.62 (1H, 1/2 AV sq., 4.8 Hz); 0.91 (6H, s); 0.97 (6H, s); 1.21 (ZN, t, 15 7.2 Hz); 1.62 (9H, s); 2.57 (2H, br. S, q, 7.2 Hz); 3.97 (ЗН, s); 4.48-4.86 (1H, m); 5.78 (1H, bw); 6.70-7.00 (ЗН, m); 7.53 (1H, m).

Example 42. Preparation of 4-oxo-3-propoxy-ethyl ethyl cinnamic acid 4-oxo-ethylbenzoic ester.

The specified connection was prepared as in example 316, however, as the 25 source material is used

cyclobranyl ester of 4-butyryloxy-3-propoxy-o-ethyl boric acid (22.1 g, 0.0297 mol) instead of cycloartenyl ester 30 of 4-butyryloxy-3-methoxy-o-ethyl-cinnamic acid, yield 17.8 g (89.1%), so pl. 140-141aC.

Specific rotation of the 3rd + 36.8 ° (from 1.00 СНС1,).

Calculated,%: C 80.31; H 10.18.

35

40

45

50

55

C45H6804 (mol.m. 672.99) Found;%: C 80.36; H 10.12. EXAMPLE 43. Preparation of 4-hydroxy-3-propoxy-aЈ-propylcinnamic acid 24-methylenecycloarthenyl ester.

The compound was prepared according to Example 316, however, the 3-prop hydroxy-4-valeryloxy-propyl cinnamic acid 24-methylene cycloartanyl ester (23.5 g, 0.0305 mol) was used instead of 4-butyryloxy-3 cycloartenyl ester -methoxy-oЈ-ethylcinnamic acid.

Yield 17.2 g (82.1%), mp. 121 ° C.

Specific rotation oOiu + 39.1 (s .1S00, CHC13).

Calculated,%: C 80.41; H 10.27.

С4ё Н7о04 (mol.m. 687.02)

Found,%: C, 80.32; H 10.34.

Examples 44-46.

a) Preparation of cycloartenyl, cyclobranyl and 24-methylene cycloCalcined,%: C 80.31; H 10.18.

five

0

five

0

five

C45H6804 (mol.m. 672.99) Found;%: C 80.36; H 10.12. EXAMPLE 43. Preparation of 4-hydroxy-3-propoxy-aЈ-propylcinnamic acid 24-methylenecycloarthenyl ester.

The compound was prepared according to Example 316, however, the 3-prop hydroxy-4-valeryloxy-propyl cinnamic acid 24-methylene cycloartanyl ester (23.5 g, 0.0305 mol) was used instead of 4-butyryloxy-3 cycloartenyl ester -methoxy-oЈ-ethylcinnamic acid.

Yield 17.2 g (82.1%), mp. 121 ° C.

Specific rotation oOiu + 39.1 (s .1S00, CHC13).

Calculated,%: C 80.41; H 10.27.

С4ё Н7о04 (mol.m. 687.02)

Found,%: C, 80.32; H 10.34.

Examples 44-46.

a) Preparation of cycloartenyl, cyclobranyl and 24-methylenecyclo4

artanyl esters of 3-butyryloxy-with ethylbenzoic acid.

These compounds were prepared as described in example 34a, where in each case Z-butyryloxy-ji-ethyl-boric acid (3.50 g, 0.0135 mol) and cycloartenol (2.85 g, 0.0067 mol), cyclobranol (2.95 g, 0.0067 mol) and 24-methylenecycloartanol (2.95 g, 0.0067 mol), respectively.

The yield (melting point and specific rotation (from 1.00; CHC1E) of each of the products are given in Table 2.

b) Preparation of cycloartenyl, cyclobranyl and 24-methylenecyclo-antenyl esters of 3-hydroxy-ti-a of ethylcinnamic acid.

These compounds were prepared as described in Example 346, wherein the compounds obtained in step a (using 0.003 mol each) are used.

The yield, melting point and specific rotation (with 1.00, CHC13) of each product are listed in Table 3.

PRI me R 47. Preparation of 4-amino-3-methoxy-benzoic acid cycloartenyl ester.

4-Acetamido-3-methoxybenzoic acid (6.5 g, 0.031 mol) in dioxa (110 ml) was reacted with thionyl chloride (21.0 ml) and then pyridine (0.5 ml) at 20 ° C. The resulting mixture stirred at 50 ° C for 5 minutes, then evaporated to dryness under reduced pressure, and a solution of cycloartenol (10.0 g, 0.023 mol) in dioxane (50 ml), benzene (50 ml) and then pyridine (20 ml). The mixture is heated at 70 ° C for 3 hours, the solvent is distilled off under reduced pressure. The residue was dissolved in chloroform (100 ml), and the chloroform solution was washed with a saturated aqueous solution of sodium bicarbonate. The aqueous solution is extracted with chloroform (5x10 ml). The entire chloroform solution is dried and concentrated under reduced pressure, and the residue is purified on a chromatographic column with silica gel (solvent: chloroform ethyl acetate (1: 1, v / v), resulting in the preparation of the cycloartenyl ester 4-acetamido-3-methoxy- zoic acid (10.8 g), yield 76.5%, mp 224-225 ° C.

8892 42

Specific rotation + 61.5 ° (with 1.00, СНС1,).

. The s-4-acetamido-3-methoxybenzoic acid cycloartenyl ester (10.0 g, 0.016 mol) is reacted with 30% HCl (20 ml) in tetrahydrofuran (200 ml) under reflux for 2 h. Then the solvent is distilled off under reduced pressure.

five

0

five

0

five

reform (300 ml), and the chloroform layer is washed successively with 1N. 5 aqueous NaOH (200 ml) and saturated brine. Aqueous solutions are extracted with chloroform three times. The combined chloroform solutions are dried and concentrated, and the residue is purified on a chromatography column with silica gel (eluent-ethyl acetate hexane 1: 4, v / v), resulting in 4-amino-3-methoxybenzoic acid 5-methyl-3-hydroxybenzoic acid (5 , 0 g), yield 58.7%, so pl. 186-187 ° C.

Specific rotation eij + 64.4 (with 1.00, СНС1,). X

Pharmacological action.

Acute toxicity tests were performed using 5 ddy male mice (30 + 2 g) and 5 Wistar male rats (100 + 2 g) for each compound by oral administration.

The following compounds are subjected to acute toxicity tests: 4-hydroxy-3-methoxybenzoic acid cycloartenyl ester (Example 8); 4-hydroxy-3-methoxy-sibenzoic acid cyclobranyl ester (Example 11); 4-hydroxy-3-methoxybenzoic acid 24-methylenecycloartanyl ester (Example 22); 3-ethoxy-4-hydroxybenzoic acid cycloartenyl ester (Example 16); 3-ethoxy-4-hydroxybenzoic acid cyclobranyl ester (Example 17); 4-oxo-3-propoxycinnamic acid cycloartenyl ester (Example 19); 3-ethoxy-4-hydroxy cinnamic acid cyclobranyl ester (Example 18); 3,4-dioxybenzoic acid cycloartenyl ester (Example 7); 3,4-dioxybenzoic acid cyclobranilate (Example 12); 3,4-dioxycinnamic acid cycloartenyl ester (Example 1); 3,4-dioxycinnamic acid cyclobranilic ester (Example 9); 3,4-Dioxycinnamic acid 24-methylenecycloartanyl ester (Example 20); ortho-hydroxybenzoic acid cycloarthenyl ester (Example 3); ortho-hydroxybenzoic acid cyclobranilic ester (Example 13); para-hydroxybenzoic acid cycloartenyl ester (Example 4); para-hydroxybenzoic acid cyclobranilate (Example 15); meta-hydroxybenzoic acid cycloartenyl ester (Example 5); 4-hydroxy-3-methoxy-oi-methylcinnamic acid cycloartenyl ester (Example 28) 4-hydroxy-3-methoxy-cЈ-methylcinnamic acid cyclobranyl ester (Example 29); 4-hydroxy-3-methoxy-cc-methylbutyric acid 24-methylenecycloartanyl ester (Example 30); 4-hydroxy-3-methoxy-ethyl ethyl hydrochloric acid cycloartenyl ester (Example 31); 3-ethoxy cyclobranyl ester of si-4-hydroxy-methylcinnamic acid (Example 35); 4-hydroxy-0Ј-ethyl-boric acid cycloartenyl ester (Example 34); 4-oxo-3-propoxy-ab-methylchloroic acid cycloartenyl ester (Example 39).

The ester compounds described and, as control drugs, cycloartenol, 24-methylene cycloartanol, cyclobrapol and jp -oridol, are forcibly administered to these mice and rats with a throat probe in doses of 0.1-5 g / kg for the mouse and 2-6 g / kg for rat. During the test, the temperature of the cage with animals is maintained in the range of 22-23 ° C. After administration, animals are observed for two weeks. At these doses, none of the animals died. Upon observation, no symptom of toxicosis and differences in behavior and body weight were found between animals tested and normal animals that were not administered the compounds. When checked after two weeks of observation, no macroscopic damage was found to any parts of the main organs. Thus, the proposed compounds have such low toxicity that it was impossible to determine the value

DTS6b.

Method A. Pharmacological testing of antihyperlipidemic activity was carried out according to two methods (A and B).

0

A. As a test animal, use the Wistar male rats (100 + 1 g, each group includes 10 rats). A diet for the control group is obtained by mixing 20% casein, 62.5% glucose, 10% hydrogenated coconut oil, 2% powdered agar, 4% salt mixture containing vitamins, 1% cholesterol and 0.5% cholic acid (Fukushima and et al., Gakugaku Lassi. 1962, 89, No. 6, p. 857-862). The diet for the test groups was obtained by thoroughly mixing 1% of each of the following compounds: cycloartenol, 24-methylenecycloartanol and cyclobranol with the diet of the control groups. Each rat was kept in an open-air cage at a constant temperature of 23 + 1 ° C and constant relative humidity for 2 weeks, during which it was given 10 g of the described ration per day. At the end, the rats were deprived of 5 meals, excluding water, for 16 hours (from 16 ° 14 day 14 for testing up to 8 ° 15 on the 15th day of testing) and after anesthesia with sodium pentobarbital (trade name Nembutal), blood was drawn from each rat from the descending abdominal aorta. Subsequently, serum levels of TC, HDL-C, TG, PL and LPO are determined.

B. Wistar male rats are used as test animals (g form groups of 8 rats and a control group of 16 rats, which give a hyperlipidemic diet). As a normal diet, a powdered diet (CE-2, manufactured by Clea Gapan Snc) is used. A hyperlipidemic diet is obtained by adding cholesterol (1%) and cholic acid (0.5%) to a normal diet. Each test compound (1%) for administration is mixed with a hyperlipidemic diet. In the aviary contain two rats, which give the described diet and water on demand. Thus, rats were fed for 4 weeks at a constant temperature of 23 + 1 ° C and a constant relative humidity of 55 + 5%. The rats are then deprived of food, but not water, for 16 hours (from 16 ° C on the 28th day of the test to 8 ° C on the 29th day of the test), are anesthetized with sodium pentobarbital, and blood is drawn from each rat through the descending abdominal aorta. After that in

0

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451

serum, TC, HDL-C, TG, PL and LPO were determined by the method described.

Method for determining total serum cholesterol (TC).

Use the vehicle from the K-set (Manufacturing Ltd). The principle of determination is as follows. The serum cholesterol ester hydrolyzes cholesterol ester hydrolase to free cholesterol and fatty acids. All free cholesterol is oxidized with cholesterol oxidase to form D4-cholestenol and hydrogen peroxide. Phenol and 4-aminoantipirin are oxidatively condensed with each other using the formed hydrogen peroxide and peroxidase. The resulting red quinone colored compound was determined colorimetrically by absorbance at 500 nm using spectrophotometry, thus determining TC.

Getting forming a coloring liquid.

Color-forming reagent (one portion) of 25,000 units. cholesterol esterase, 25 units. cholesterinoxydazy, 3554 units peroxidase, 20 mg of 4-aminoantipyrin.

Buffer solution: 100 ml of a solution containing phenol (33.3 mg), potassium dihydrogen phosphate (489.9 mg) and anhydrous sodium hydrogen phosphate (908.5 mg) in purified water.

Standard solution: 100 ml of solution containing cholesterol (300 mg).

A solution of one portion of the color-forming reagent in 160 ml of buffer solution is called a color-forming liquid.

The coloring liquid (3.0 ml) is mixed thoroughly with a serum sample (0.02 ml). The mixture is heated once at 37 ° C for 15 minutes and the absorbance at 500 nm is measured with a spectrophotometer. The absorption found is designated as EA. In addition, the color forming liquid (3.0 ml) is thoroughly mixed with a standard solution. The mixture is processed and the absorbance is measured at 500 nm in the same manner as described above. Found absorption is designated as ES. Both EA and ES are determined based on the result of the blank / experience,

ten

0

892

46

carried out using a single coloring liquid (3.0 ml),

EA The value of TS is x 300 mg / dL.

Method for determining serum concentration of high-density lipoprotein cholesterol (HDL-C).

HDL-C from the N-kit (manufactured by Nippon Shoji kaisha Ltd) is used. Ultra-high-density lipoprotein (VLDL) and low-density lipoprotein (LDL) are precipitated from serum by the action of heparin. The precipitate is separated by centrifuging. High lipoprotein

five

0

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0

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density (HDL) is dissolved in the separated supernatant. The cholesterol esters of this fraction hydrolyze cholesterol ester hydrolase to free cholesterol and fatty acids. All free cholesterol is oxidized by cholesterol oxidase to form d-cholestenol and hydrogen peroxide. Phenol and 4-aminoantipirin are oxidatively condensed with each other using the formed hydrogen peroxide and peroxidase. The resulting red quinone colored compound was measured colorimetrically by absorbance at 500 nm using a spectrophotometer, thus determined by HDL-C.

Method for determining total serum phospholipid concentration (PL).

PL from K-kit (manufactured by Nippon Kais-, ha, Ltd) is used for the determination. Lecithin, sphingomyelin, and lysolecithin are decomposed by phospholipase to choline and, respectively, to phosphatidic acid, N-acylophosphine phosphate, or lysophosphatidic acid. The resulting choline is quantitatively decomposed by choline oxidase to hydrogen peroxide and betaine. With this hydrogen peroxide and peroxidase, phenol and 4-amino-antipyridine are condensed to form a red quinone pigment, after which the absorbance at 500 nm is measured on a spectrophotometer and thus the PL is determined.

Method for determining total serum triglyceride (TG) concentration.

The serum TG content is determined using a triglyceride test kit (manufacture

47

Wako Pure Chemical Industries, Ltd), in which acetylaetonone is used as a reagent in a decreasing manner.

Whey proteins are precipitated by mixing isopropyl alcohol and a serum sample. At the same time, serum lipids and saccharides are extracted into the isopropyl alcohol mixture. An adsorbent is added to the solution in isopropyl alcohol to adsorb compounds that interfere with staining. After centrifuging the mixture, potassium hydroxide was added to the supernatant, washing the triglyceride and releasing glycerin. Thereafter, the pH of the mixture is adjusted to 6 by adding a buffer solution and a solution of sodium metaperiodate is added to oxidize glycerol to formic acid (1 mole of 1 mole glycerol) and formaldehyde (2 mole of 1 mole glycerol). The resulting aldehyde is allowed to react with acetylacetone and ammonia in a buffer solution to form the cyclic compound 3,5-diapethyl-1,4-dehydrobutidine. This yellow momentum is determined by measuring the absorbance at 410 nm on a spectrophotometer, and thus the TG content is determined.

Method for determination of total lipid peroxide concentration (LPO) in serum.

For this definition, a lipid peroxide test kit (manufactured by Wako Pure Chemical Co., Ltd.) is used according to the Yagi method based on the use of thiobarbituric acid (K.Jagi. Biochem, Med, 1976., 15, p. 212. Vitamin. 1975 , 49, p. 403), a physiological saline solution (1.0 ml) is added to a serum sample (0.05 ml) and the mixture is gently stirred. After centrifuging (3000 rpm, 10 min) the mixture and the supernatant (0.5 ml), 12N sulfuric acid (4.0 ml) are added and thoroughly mixed. A 10% aqueous solution of phosphotungstic acid (0.5 ml) is added and the mixture is thoroughly mixed, left to stand for 5 minutes, and centrifuged at 3000 rpm for 10 minutes. The resulting precipitate is carefully suspended in a mixture

to

g-

, - 55

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1 / 12n. sulfuric acid (2.0 ml) and a 10% aqueous solution of phosphorus-tungstic acid using a mixer. Then the suspension is centrifuged at 3000 rpm for 10 minutes, after which the resulting precipitate is suspended in distilled water (4.0 ml) using a stirrer. Thereafter, TE A-Reagent (1.0 ml, 50% acetic acid solution containing thiobarbituric acid) is mixed thoroughly with the suspension. The mixture is placed in a centrifuge tube and heated in a boiling water bath for 60 minutes with a glass bottle covering the top of the tube. After cooling the tube in running water for 5 min to

2, butanol (5.0 ml) was added to the mixture and, after securing the tube, they were thoroughly mixed for 20 seconds using a mixer, thus conducting the extraction of the reaction product to

25 butanol. The mixture is centrifuged at 3000 rpm for 10 minutes. The fluorescence of the bootal layer is measured. After determining the zero point, an empty experiment is measured.

30 fluorescence intensity (F) 0.1 ml of a standard solution (1,1,3,3-tetraethoxypropane, 5 mmol / ml fluorescence intensity of sample f at 553 nm and at an excitation radiation wavelength of 515 nm).

35 Thus, in this method, the product of the reaction of LPO with thiobarbituric acid is identical to the product of the reaction of malondialdehyde with thiobarbituric acid. Accordingly, the LPO concentration is defined as the amount of malondialdehyde in 1 ml of serum. The standard solution is a 5 nmol / ml aqueous solution of 1,1,3,3-tetraethoxyprop40

45

goes to malondialdehyde. Since this procedure uses 0.1 ml of the standard solution, the amount of 1,1,3,3-tetraethoxypropane is 0.5 nmol. Then the content of LPO (nmol / ml serum calculated by the following equation:

l, f 1.0 1.05 f ° 5 x f x x f x

21.

Anterogenic indicator (AI) is defined as (TC-HDL-C) LDL-C

49

The results of pharmacological tests for hypolipidemic activity.

The lipid-lowering effect of the proposed compounds on serum lipids and on serum lipids hydroperoxides. The compounds selected for this are the same compounds that were selected for the description of acute toxicity. The tests were carried out as described, in which rats were fed a diet high in cholesterol.

Testing of the known compounds cycloartenol, 24-methylenecycloartanol, and cyclobranol has been performed in order to evaluate the anti-hyperlipidemic effect of the indicated agents.

The test results on the hypolipidemic activity of cycloartenol, cyclobranol and 24-methylenecycloartanol, which were used as control drugs, are shown in Tables 4 and 5 (according to the Iv method, Tables 18 and 19 (according to Method B and summarized as follows The effects of using both test methods are basically identical. A decrease in total serum cholesterol (TC) was observed for both groups of animals who were given a diet with an increased x olesterol containing cycloarthenol and given a diet with a high cholesterol content containing cyclobranol, with significant values of decrease (p 0.05 according to method A, and 01 according to method B) compared to the control group of animals that had a diet, containing only an increased amount of cholesterol. Lowering total cholesterol (TC) in the case of using 24-methylenecycloartanol is insignificant and did not give significant values according to method A, while giving significant values according to method B (, 05). As for HD L-C, cycloartenol lowers its content by a significant amount (, 05 according to method A and P 0.01 according to method B), 24-methylenecycloartanol lowers it slightly, so that as a result of using equipment

ten

15

20

25

889250

their testing methods yield insignificant values. Cyclobranol shows, on the contrary, a tendency to increase HDL-C content quite significantly.

The proposed compounds are hypolipidemic agents that can significantly lower total cholesterol and increase HD L-C in serum. Any of triterpenyl alcohols, such as cycloartenol, cyclobranol or 24-methylenecycloartanol, when used alone, significantly reduces the level of total cholesterol in serum. However, when testing them, no increase in HDL-C was observed when the hypolipidemic effect was achieved according to method A or according to me. Todu V.

Cycloartenol and cyclobranol show a tendency to decrease the AI index according to method A, as well as 24-methylenecycloartanol exhibits only a slight tendency to increase the AI. According to the testing method B, all three trypteric alcohol show a tendency to decrease the atherogenic indicator AI. As the values of TG, PL, and L PO are absorbed, then when testing in both ways all three alcohols do not give any significant change in the values of these indicators.

If we compare the effects of these three triterpenyl alcohols, it should be noted that cyclobranol has a tendency to decrease TC, AI, TG, PL and LPO, but increases HDL-C, and, therefore, it has an effect different from cycloartenol and 24- methylene chloroethanol. At the same time, it can be stated that cyclobranol exceeds cycloartenol and 24-methylenecycloartanol in hypolipidemic effects.

The lipid-lowering action of the proposed compounds, tested according to method A, is presented in table. 6-17.

The action of the proposed compounds and the action of cycloartenol, cyclobranol, 24-methylenecycloartanol oryzanol, used as 30

35

40

45

50

55

51

the test drugs tested according to method B are shown in the table „20,21

Tab. 20-23 show that TC, PL and LPO in the normal diet group (denoted as N) are highly reliably suppressed (p with 0.001), except for HDL-C, which rises with high certainty (, 001), in contrast to the control group fed on a hyperlipidemic diet (denoted as C). TG tendencies are suppressed in N shown in C, but this TG difference in N and C is not significant.

The lipid-lowering effect of the improved serum lipid components is clearly seen in the groups that feed on a hyperlipidemic diet, each containing the proposed compounds or each of the control drugs, compared to this action in a group that feeds only on a hyperlipidemic diet. In particular, the proposed compounds have a significantly better effect on two or more of the lipid components of the TC, HDL-C} PL and LPO, than the control compounds. I According to method A, the content of TC varies with the proposed compounds as follows. The compounds of examples 11,17,18,7,12,3,13,4,15 and 27 reduce the level of TC with medium confidence. The compounds of examples 8,22,16,19,9 and 5 reduce the concentration of TC with low confidence (pCO, 05). The compounds of examples 1 and 20 do not significantly reduce the concentration of TC, but show

downward trend 1

In method B, the level is reduced by control drugs, i.e., three triterpenilic alcohols and J1-oryzanol, with moderate confidence (, 01) compared with the level of TC in the control group that received only a hyperlipidemic diet. In contrast, the compounds of Examples 28, 29, and 30 suppressed the TC level with high confidence (p −0.001). The compounds of Examples 31,35,34 and 39 reduce the level of TC with medium confidence (p 0.01).

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The content of HDL-C in method A is varied by the proposed compounds as follows.

The compound of example 3 increases the HDL-C content with high confidence (p-0.001), the compounds of examples 11,17 and 12 with medium confidence (, 01), and the compounds of examples according to examples 18,7 and 13 with low confidence (, 05). The compounds of Examples 22, 19, 4, and 5 slightly change or slightly reduce the HDL-C content, and

15 other examples show a tendency to slightly increase this content.

In method B, the effect of test compounds on HDL-C is as follows.

2Q Control drug - cycloartenol causes a decrease with high confidence (, 01), while other control drugs - cyclobranol, 24-methylenecycloartenol

25 and fr-orizanop tend to slightly increase or decrease the content. In contrast, the compounds of examples 28,29,30,35 and 39 with high reliability

30 (0,001) increase the content

HDL-C, and the compounds of examples 31 and 34 increase with moderate confidence (, 01). In particular, the compounds of Examples 29, 30, and 35 cause a marked increase in HDL-C content compared with the group on the normal diet.

All compounds, without exception, show a clear tendency to suppress the level of AI in methods A or B.

In method A, the TG content does not decrease reliably, but remains unchanged or slightly reduced by all tested compounds, except that the compound of Example 27 reduces the content with low confidence (, 05). In method B, the proposed compounds, as well as the control drugs, tend to suppress TG slightly or to some extent, but not significantly

In method A, the compounds according to examples 17,18,7,12,3,13,27 reliably reduce the level of PL (p 10.001), the compounds of 55 denis according to examples 8,11,16,19 and 15 decrease with medium confidence ( p.4 0.01), and the compounds according to examples 22.9 and 4 - with the level of sufficient 35

40

5315

nosti, 05. The compounds of examples 1.20 and 5 show a clear tendency to decrease the level, but not significantly.

In the case of Control B, the drugs show a tendency to slightly decrease the PL level, but not significantly. In contrast, the compounds of Examples 28, 29, 30, 35, and 39 reduced the PL content with a p-dO level of confidence, 001, the compounds of Examples 3t and 39 decreased with a confidence level, 01.

In method A, compounds using ttrimers 4 and 15 reduce the level of LPO with a certainty, 001, and compounds of examples 8, 11, 16, 17, 18, and 5 with a level of confidence, 05 Other proposed compounds show a distinct tendency to decrease but slightly. In method B, the control drug - -oranol reduces the LPO level with confidence, 01, and the control drugs, which are triterfoes

Lovy alcohols show a pronounced tendency to decrease, but insignificant. In contrast, the compounds of Examples 28,29,30,31,35,32,34 and 39 reduce the level of LPO with a p accuracy of 0.001.

 Most of the proposed compounds in tests in method A or B show a clear tendency to increase HDL-C content and reduce levels of TC, AT, PL and IPO. A comparison with the effects observed with the introduction of free triterpene alcohols alone shows that the hypolipidemic activities of the proposed compounds are synergistic effects.

The increase in body weight of the rats used for tests for hypolipidemic activity in method B is shown in Table 7-1. The body weight of rats receiving a normal diet increased significantly (p 4 0.001) compared with the body weight of rats in the control group receiving a hyperlipidemic diet. Groups of rats receiving a hyperlipidemic diet containing each of the control drugs show a slight increase in body weight, but not significant, compared with the control group of rats receiving only a hyperlipidemic diet.

54

When determining the antihyperlipidemic activity according to method A, the daily dose of each of the proposed compounds is 1% at 10 g / day of a hyperlipidemic diet, i.e. 100 mg.

In Method B, the dose of each of the proposed compounds was approximately calculated as 210 mg / day for each rat, mainly from the amount of diet consumed containing the compound. For example, 4-hydroxy-3-methoxy-A-methylcinnamic acid cyclo-artenyl ester (Example 28), 3-ethoxy-4-oxo-3-methylcinnaric acid cyclobraniline ester (Example 35) contain a correspondingly bound 4-hydroxy -3-methoxy--methyl coric acid (70.8 mg), 3-ethoxy-4-hydroxy-methyl trichroic acid (72.5 mg).

Each of these organic acids in free form is added to the hyperlipidemic diet and the resulting diet is administered to rats.

0

five

five

0

antihyperlipidemic activity, however

0 higher doses of free acids (59.4-72.5 mg / day) and no nigperlipidemic effect. Thus, it has been established that organic acids, which are released as a result of hydrolysis of tryphenyl ester of an organic acid, are not involved in the action of the proposed compounds.

In tab. 5-26 accept the following notation.

Compound C - serum of the control group of 10 rats receiving a hyperlipidemic diet, in table. 5 through 26, compound 1 is the serum of a group of 10 rats receiving a hyperlipidemic diet containing 1% cycloartenol as a control drug, in table. 5 and 6, Compound 2 — Serum from a group of 10 rats treated with a hyperlipidemic diet containing 1% cyclobranol as a control drug, in Table. 5 and 6, compound 3 - serum of a group of 10 rats treated with hyperlipidemia

A 5-day diet containing 1% 24-methylenecycloartanol as a control drug, in Table. 5 and 6. SD is the standard deviation.

five

551

Raen. means the difference Q - Qc a diff. means (Q - Qc) x 100 / QC, where Q is the concentration of the lipid component in a serum sample; Qc is the concentration of the lipid component in the serum of the control group ..

In the examples, a serum of a group of 10 rats fed a hyperlipidemic diet, containing 1% of the compound according to each of the examples, in the table. 6-26.

Compound C - serum of the control group of 16 rats treated with hyperlipidemic diet, in table. 18-26, compound 1 - serum of a group of 8 rats treated with a hyperlipidemic diet containing 1% cycloartenol as a control drug, in table. 18-21 and 26, Compound 2 — Serum from a group of 8 rats receiving a hyperlipidemic diet containing 1% cyclobranol as a control drug, in Table. 18-21 and 26, Compound 3 — Serum from a group of 8 rats treated with a hyperlipidemic diet containing 1% 24-methylenecycloartanol as a control drug, in Table. 18-21 and 26.

In tab. 20 Compound N - Serum from a group of 8 rats that received a normal diet (this also applies to the following tables), Compound 4 - Serum from a group of 8 rats that received a hyperlipidemic diet, containing 1% orsanol, according to examples - serum from a group of 8 rats, receiving a hyperlipidemic diet, containing 1% of the compound in each of the examples, in table. 20-26.

This also applies to the following tables.

Thus, the proposed method makes it possible to obtain new triperpenyl esters of organic acids, which have a higher antiperlipidymic activity.

Claims (1)

Invention Formula The method of producing triterpenyl esters of organic acids of general formula 56 ten 15 | 0 five 0 where R, is the group COO R &, CH CRSCOOR; R2 is H, OH-group; R3 is H, OH groups, coxy; R - H, OH groups, amino; Rg- - H, C, -C4-alkyl; R is cycloartenyl, cyclobranyl, 24-methylenecycloartanyl, and the substitution in the benzene ring can be a pair selected from the row OH group and C, -C.-alkoxy group, amino group and C1-C-alkoxy group, two OH groups, with the exception of ferulic acid triterpenyl esters, or at least one of the radicals R2 and RJ. is an OH group or R4 is an amino group, characterized in that the triterpenyl alcohol ester of the general formula 35 Where Rr has the indicated meanings; -H, C-Sy-acyloxy; -H, C (-C4-alkoxy-, acyloxy-; H, Cr-C6 acyloxy-, Cr-C5 acylamido, and the substitution in the benzene ring may be a pair selected from the series Cr-C6-acyloxy- and C, -C-alkoxy-, C2-C-acylamido- and C, -C4-alkoxy-, two C2-C6 acyloxygroups, and at least one from the radicals Rr and C-Su-acyloxy or the radical R-acylamido - Cr-C -group, is deacylated. 57 153889258 Table 1 The confidence level pi 0.05. Spreadsheets Table3 Table Table/ Tables Table 10 -16.7 -10.0 -0.2 -0.3 C205.1 127.4 81.5 ± 10.1 27166.7 ± 28,194.1 9.3 , 01. .001. 27 -38.4 -18.7 +15.1 + 18.5-0.745 -49.1 -12.7 -37.0 -30.6 -17.6 -0.68 -29.8 32-122.1 -34.7 +0.1 +1.2 -38,1 -37,7 -37,8 -3.2 -23.7 -4.3 +1.5 +11.1 -9.8 -0.7 -5.2 -7.0 Table 13 -0.276 -14.9 -0.8 -3.2 -8.0 -5.4 -0.31 -13.2 T and in l to c and 14 34,, 173.6 ± 11.0 21 ,,, 0 ± 10.6 2.27 -0.38 1.59 0.33 Table 15 Table 17 -17.6 -38.9 +1.9 +3.8 -36.7 -24.0 Table 19 -2.5 -2.3 -5.5 -3.9 -5.7 -9.2 -1.6 -0.12 -2.7 -0.20 -6.5 -0.09 -4.3 -7.1 -3.2 , 05. , 01. , 001. Table 20 Table 23 C418.4 ± 176.2 16.0 te, N53.0 -7.327.4 ± 4.1 25.15 81.3 46.0 176.8 -52.1 3.47 0.34 0.934 53.2 ± 21.1 94.4 ± 12.2 1.15 ± 0.12 , 001. -365,4 -8,7 +11.4 +71.3 -24.22 -96.3 -28.1 -34.6 -82.4 -46.6 -2.32 -66.9 p iO.001. T a b l and c a 24 Table 25